Absorption and Excretion of Luteolin and Apigenin in Rats after Oral Administration of <i>Chrysanthemum morifolium</i> Extract

Chen, Ting; Li, Liping; Lu, Xin-Yan; Jiang, Huidi; Zeng, Su

doi:10.1021/jf062088r

Cited by 121 publications

(121 citation statements)

References 22 publications

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“…It has been reported that apigenin is metabolized to luteolin in vivo and that their elimination half-lives in rat are only 1.75 ± 1.18 and 0.97 ± 1.25 h, respectively (40). However, a study of oral Chrysanthemum morifolium extract, which contains apigenin and luteolin, showed that both flavonoids have a quick absorption and a slow elimination phase, with apigenin absorbed more efficiently than luteolin in herbal extract, and suggested a possible accumulation of both flavonoids in vivo (41). We administered the single compounds and formula using the same vehicle as reported for apigenin (15).…”

Section: Discussionmentioning

confidence: 99%

Herbal Extract ofWedelia chinensisAttenuates Androgen Receptor Activity and Orthotopic Growth of Prostate Cancer in Nude Mice

Tsai

Lin

Yang

et al. 2009

Clinical Cancer Research

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Purpose: Wedelia chinensis is a common ingredient of anti-inflammatory herbal medicines in Taiwan and southern China. Inflammation is involved in promoting tumor growth, invasion, and metastasis. This study aims to test the biological effects in vivo of W. chinensis extract on prostate cancer. Experimental Design: The in vivo efficacy and mechanisms of action of oral administration of a standardized extract of W. chinensis were analyzed in animals bearing a subcutaneous or orthotopic prostate cancer xenograft. Results: Exposure of prostate cancer cells to W. chinensis extract induced apoptosis selectively in androgen receptor (AR)-positive prostate cancer cells and shifted the proportion in each phase of cell cycle toward G 2 -M phase in AR-negative prostate cancer cells. Oral herbal extract (4 or 40 mg/kg/d for 24-28 days) attenuated the growth of prostate tumors in nude mice implanted at both subcutaneous (31% and 44%, respectively) and orthotopic (49% and 49%, respectively) sites. The tumor suppression effects were associated with increased apoptosis and lower proliferation in tumor cells as well as reduced tumor angiogenesis. The antitumor effect of W. chinensis extract was correlated with accumulation of the principle active compounds wedelolactone, luteolin, and apigenin in vivo. Conclusion: Anticancer action of W. chinensis extract was due to three active compounds that inhibit the AR signaling pathway. Oral administration of W. chinensis extract impeded prostate cancer tumorigenesis. Future studies of W. chinensis for chemoprevention or complementary medicine against prostate cancer in humans are thus warranted. (Clin Cancer Res 2009;15(17):5435-44) Carcinoma of the prostate gland is the most common malignancy in males in the western world (1). Despite the low incidence of prostate cancer in oriental countries, statistics from Taiwan reveal prostate cancer deaths have continued to increase in the past two decades.5 Androgen ablation therapy remains the most effective means of treating metastatic prostate cancer tumors (2, 3). This therapy often induces apoptosis in the majority of prostate cancer cells by blocking testosterone signaling at the androgen receptor (AR) and lowering the expression of AR-regulated genes including prostate-specific antigen (PSA), a serologic biomarker up-regulated by androgens (4, 5). The CWR22 tumor model, based on implantation of a human prostate cancer in an athymic nude mouse, progresses in the same androgen-dependent manner as observed in clinical prostate cancer tumors. Further development from castrationrelapsed CWR22 tumors created subline tumors and a cell line, 22Rv1, which retain expression of AR and show androgen stimulation of neoplasia (6, 7). Earlier, we devised the androgeninduced PSA-luciferase activity in prostate cancer 22Rv1 cells and a derived stable clone, 103E, as a cell-based assay to detect any AR modulator effect of herbal extract or compounds (8-10). To determine whether herbal remedies or compounds can inhibit prostate cancer growth in o...

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Section: Discussionmentioning

confidence: 99%

Herbal Extract ofWedelia chinensisAttenuates Androgen Receptor Activity and Orthotopic Growth of Prostate Cancer in Nude Mice

Tsai

Lin

Yang

et al. 2009

Clinical Cancer Research

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“…The concentration of luteolin in plasma samples was determined by a previously published method with minor modifications (23,24). Briefly, 100 μl of 6.0% perchloric acid was added to 100 μl plasma sample to precipitate protein.…”

Section: Hplc and Lc/ms/ms Assaymentioning

confidence: 99%

Pharmacokinetic Interaction between the Flavonoid Luteolin and γ-Hydroxybutyrate in Rats: Potential Involvement of Monocarboxylate Transporters

Wang

Morris

2008

AAPS J

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Abstract. Monocarboxylate transporter 1 (MCT1) has been previously reported as an important determinant of the renal reabsorption of the drug of abuse, γ-hydroxybutyrate (GHB). Luteolin is a potent MCT1 inhibitor, inhibiting the uptake of GHB with an IC 50 of 0.41 μM in MCT1-transfected MDA-MB231 cells. The objectives of this study were to characterize the effects of luteolin on GHB pharmacokinetics and pharmacodynamics in rats, and to investigate the mechanism of the interaction using model-fitting methods. GHB (400 and 1,000 mg/kg) and luteolin (0, 4 and 10 mg/kg) were administered to rats via iv bolus doses. The plasma or urine concentrations of luteolin and GHB were determined by HPLC and LC/MS/MS, respectively. The pharmacodynamic parameter sleep time in rats after GHB administration was recorded. A pharmacokinetic model containing capacity-limited renal reabsorption and metabolic clearance was constructed to characterize the in vivo interaction. Luteolin significantly decreased the plasma concentration and AUC, and increased the total and renal clearances of GHB. Moreover, luteolin significantly shortened the duration of GHB (1,000 mg/kg)-induced sleep in rats (161±16, 131±14 and 121±5 min for control, luteolin 4 and 10 mg/kg groups, respectively, p<0.01). An uncompetitive inhibition model, with an inhibition constant of 1.1 μM, best described the in vivo pharmacokinetic interaction. The results of this study indicated that luteolin significantly altered the pharmacokinetics of GHB by inhibiting its MCT1-mediated transport. The interaction between luteolin and GHB may offer a potential clinical detoxification strategy to treat GHB overdoses.

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“…Furthermore, the absorption and excretion of flavonoids will play an important role on the effects of flavonoids in vivo. In a previous report, it was shown that luteolin in Chrysanthemum morifolium extract was absorbed sufficiently in a rat model and the cumulative luteolin excreted in the urine and feces were 37.9% of the dose during 72 h after oral administration (32). It was explained that much of the luteolin might be metabolized to simple compounds or accumulated in the tissues.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Luteolin on an Oxidative-Stress Model Induced by Microinjection of Sodium Nitroprusside in Mice

et al. 2013

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Abstract. Accumulating lines of evidence showed that luteolin, a polyphenolic compound, has potent neuroprotective effects. The purpose of this study was to examine whether luteolin can protect against sodium nitroprusside (SNP)-induced oxidative damage in mouse brain. Intrastriatal co-injection of luteolin (3 -30 nmol) with SNP (10 nmol) dose-dependently protected against brain damage and motor dysfunction. Oral administrations of luteolin (600 -1200 mg/kg) dosedependently protected against brain damage and motor dysfunction induced by striatal injection of SNP. Furthermore, luteolin (30 -100 M) concentration dependently protected against Fe 2+ -induced lipid peroxidation in mouse brain homogenate. Luteolin (1 -100 g/ml) showed potent DPPH radical scavenging ability, when compared with ascorbic acid and glutathione. Finally, a ferrozine assay showed that luteolin (30 -100 g/ml) has Fe 2+ -chelating ability, but this was weaker than that of ethylenediaminetetraacetic acid. These results suggest that intrastriatal or oral administration of luteolin protected mice brain from SNP-induced oxidative damage by scavenging and chelating effects.

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Absorption and Excretion of Luteolin and Apigenin in Rats after Oral Administration of Chrysanthemum morifolium Extract

Cited by 121 publications

References 22 publications

Herbal Extract ofWedelia chinensisAttenuates Androgen Receptor Activity and Orthotopic Growth of Prostate Cancer in Nude Mice

Herbal Extract ofWedelia chinensisAttenuates Androgen Receptor Activity and Orthotopic Growth of Prostate Cancer in Nude Mice

Pharmacokinetic Interaction between the Flavonoid Luteolin and γ-Hydroxybutyrate in Rats: Potential Involvement of Monocarboxylate Transporters

Protective Effect of Luteolin on an Oxidative-Stress Model Induced by Microinjection of Sodium Nitroprusside in Mice

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